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Combination IFNß and Membrane-Stable CD40L Maximize Tumor Dendritic Cell Activation and Lymph Node Trafficking to Elicit Systemic T-cell Immunity.
Zheng, Hong; Yu, Xiaoqing; Ibrahim, Mohammed L; Foresman, Dana; Xie, Mengyu; Johnson, Joseph O; Boyle, Theresa A; Ruffell, Brian; Perez, Bradford A; Antonia, Scott J; Ready, Neal; Saltos, Andreas N; Cantwell, Mark J; Beg, Amer A.
Afiliação
  • Zheng H; Department of Immunology, Moffitt Cancer Center, Tampa, Florida.
  • Yu X; Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida.
  • Ibrahim ML; Department of Immunology, Moffitt Cancer Center, Tampa, Florida.
  • Foresman D; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
  • Xie M; Department of Immunology, Moffitt Cancer Center, Tampa, Florida.
  • Johnson JO; Department of Immunology, Moffitt Cancer Center, Tampa, Florida.
  • Boyle TA; Analytical Microscopy, Moffitt Cancer Center, Tampa, Florida.
  • Ruffell B; Pathology, Moffitt Cancer Center, Tampa, Florida.
  • Perez BA; Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida.
  • Antonia SJ; Department of Immunology, Moffitt Cancer Center, Tampa, Florida.
  • Ready N; Radiation Oncology, Moffitt Cancer Center, Tampa, Florida.
  • Saltos AN; Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina.
  • Cantwell MJ; Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina.
  • Beg AA; Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida.
Cancer Immunol Res ; 11(4): 466-485, 2023 04 03.
Article em En | MEDLINE | ID: mdl-36757308
ABSTRACT
Oncolytic virus therapies induce the direct killing of tumor cells and activation of conventional dendritic cells (cDC); however, cDC activation has not been optimized with current therapies. We evaluated the adenoviral delivery of engineered membrane-stable CD40L (MEM40) and IFNß to locally activate cDCs in mouse tumor models. Combined tumor MEM40 and IFNß expression induced the highest cDC activation coupled with increased lymph node migration, increased systemic antitumor CD8+ T-cell responses, and regression of established tumors in a cDC1-dependent manner. MEM40 + IFNß combined with checkpoint inhibitors led to effective control of distant tumors and lung metastases. An oncolytic adenovirus (MEM-288) expressing MEM40 + IFNß  in phase I clinical testing induced cancer cell loss concomitant with enhanced T-cell infiltration and increased systemic presence of tumor T-cell clonotypes in non-small cell lung cancer (NSCLC) patients. This approach to simultaneously target two major DC-activating pathways has the potential to significantly affect the solid tumor immunotherapy landscape.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cancer Immunol Res Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cancer Immunol Res Ano de publicação: 2023 Tipo de documento: Article